{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:04:00Z","timestamp":1779775440643,"version":"3.53.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aims to investigate the effects of metformin on T cell differentiation and the underlying mechanisms in NOD\/Ltj mice, a model for primary Sj\u00f6gren's syndrome (pSS). Specifically, we focus on metformin's role in modulating Th17 differentiation and its potential regulation through the mTOR\/STAT3 signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established a metformin\u2010treated pSS mouse model. Salivary flow rate, histological analysis, and flow cytometry were employed to assess inflammation and T cell subsets. Cytokine secretion was measured using qPCR, ELISA, and Western blot analysis. To investigate the molecular pathways involved, we examined mTOR\/STAT3 signaling and administered mTOR and STAT3 agonists.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Metformin treatment significantly alleviated salivary gland inflammation and increased salivary flow in pSS mice. Flow cytometry showed that metformin reduced the proportions of Th1, Th2, and Th17 cells, while increasing Treg cells. The reduction in Th17 cells was the most prominent. Furthermore, metformin decreased the levels of pro\u2010inflammatory cytokines (IL\u201021, IL\u201022, IFN\u2010\u03b3) and increased anti\u2010inflammatory cytokines (IL\u20104, IL\u201010). Immunohistochemistry and Western blot analysis demonstrated that metformin inhibited IL\u201017 expression. Additionally, metformin treatment suppressed the mTOR\/STAT3 signaling pathway, and mTOR\/STAT3 agonists reversed the effects of metformin on Th17 differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Metformin effectively modulates T cell differentiation and alleviates pSS symptoms, primarily by suppressing Th17 cell differentiation through the mTOR\/STAT3 pathway. These findings provide insights into the therapeutic mechanisms of metformin in pSS and suggest its potential as a treatment strategy for immune\u2010mediated diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1756-185x.70669","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:10:00Z","timestamp":1777900200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin Suppress Th17 Differentiation and Function to Improve Glandular Function in Primary Sj\u00f6gren's Syndrome"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5219-4470","authenticated-orcid":false,"given":"Jian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology The First Affiliated Hospital of Bengbu Medical University  Bengbu Anhui Province 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